rohanpurohit

INTRODUCTION

As we all know that cells are the structural and functional unit of living organisms. They are the building blocks of the body. But what if this smallest unit of living beings started to grow unnaturally or never stops growing, sounds a bit strange?

In simple words the cell is immortal, but there’s a catch, the body in which the cell grows in such a manner would not be designed to transform according to the growth of the cells and would create severe complications and also may prove to be fatal for humans. This field of biomedical research has extreme potential and also may lead to unlocking many secrets about the human body.

IMMORTALISED CELL LINES

Immortalized cell lines are the group of special mutated cells (can be natural as well as induced externally) that divide unconditionally without any cellular senescence period. As because they can be grown for a prolonged period, therefore these cells are perfectly suited for in vitro experiments. Immortal tool lines are an important field to research on and together with the help of biochemistry and cell biology the field has huge potential. The mutation by which the cell grows infinitely can be introduced artificially with the help of biotechnology.

As the immortalized cell divide indefinitely but should not be confused with stem cells which also divide infinitely but forms normal body parts.

NATURAL BIOLOGY AND PATHOLOGY

Natural cell lines come in various types

• Some are natural cell lines that are derived from stem cells.
• Whereas some are cancerous.

CANCEROUS CELLS

When a somatic cell somehow mutates mostly due to carcinogens and the cancerous gene gets activated the cells divide almost infinitely and this causes deregulation in the normal cell cycle. The origin of some immortalized cell lines is also from this type of cancerous cell. The most famous one being the HeLa human cell that was extracted from Henrietta lacks without her consent in 1951 at Johns Hopkins Hospital, Baltimore, Maryland.

HeLa cell AND THE REVOLUTION

Henrietta lacks a poor girl from Virginia went to John Hopkins hospital as she was feeling some abdominal discomfort when diagnosed it was discovered that she had cancer in her cervical region. She died while fighting it but the doctor extracted her tumour cells before her death for some personal research purpose.

When he was studying the cell in a test tube he found out an amazing thing that would change medical science forever, the cells extracted from the deceased also grew outside the body in a test tube. This was the first cancer cell to behave in such a manner. For which it was later named immortalized human cell line and that special cell was known as HeLa cell, named after Henrietta Lacks.

This thing totally changed the whole scene of modern biomedical research now scientists all over the world can carry on human experiments without a human. Starting from the impact of human gravity on space to testing the human body with radiation and its side effects all these things now could be done without any risk. The immortalized human cell line was also used by scientists all over the world to understand cancer and its repercussions on the human body and adjacent cells.

HeLa cell AND COVID-19:

 Before the 21^st century, the world was affected and struggling with a fatal viral disease called polio. This was the time when the HeLa cell was first used to study the virus and make a vaccine for it. For its amazing contribution now most of the globe is vaccinated and hence free from the deadly poliovirus.

After this HeLa cell has been used to study many viruses and their effects on human cells. The most recent one being COVID 19, Hela cells were being used to study the way COVID 19 infects the body and its mechanism. In recent research found an astonishing fact that coronavirus was unable to infect the HeLa cells. Searching the reason for the same scientist found that was due to lack of a molecule in the HeLa cell called the A2EC molecule. After the groundbreaking discovery, a few tweaks were made with the HeLa cell and the A2EC molecule was engineered to be inserted in the cell after which the COVID 19 virus was able to enter the cell and carry its biochemical mechanisms(i.e.-to get embedded in the genome and divide using the host cellular functions.

USES OF IMMORTALISED CELL LINES

• Used as a simple model to study and research complex biological body parts
• Used in its research for immortality, as the cells can grow indefinitely in a culture they can be used to propagate more cells for studying in labs without any limitations.
• Can help to give rise to a big clonal population which in turn will be used to study
• Used in biotechnology as a cost-effective way of growing multicellular cells for testing various things like drugs, toxicity, etc.

LIMITATIONS OF IMMORTALISED CELL LINES

 Changes from non-immortal origins

Immortalized cell lines often originated from a well-known tissue type, they have undergone significant mutations to become immortal. This technique can change the configuration of the cell. Further, cell lines can change genetically over multiple passages, leading to phenotypic differences among isolates and potentially different experimental results depending on when and with what strain isolate an experiment is conducted.

Contamination with other cells

During biomedical research, the cells that are used to study are often contaminated by more aggressive cells. For example, supposed thyroid lines were melanoma cells, supposed prostate tissue was bladder cancer, and supposed normal uterine cultures were breast cancer.

METHODS OF GENERATION  

1. Isolating cells from naturally occurring cancer. This method is the original method that was first used to extract immortalized cells. Also know a HeLa; the cells were derived from the patient’s cervix as she was suffering from cervical cancer.
2. Another method is by the introduction of a viral gene that deregulates the cell cycle(e.g. the adenovirus type 5 E1 gene was used to immortalize the HEK 293 cell line; the Epstein-Barr virus can immortalize B lymphocytes by infection).
3. Another method is by the introduction of a viral gene that partially deregulates the cell cycle (e.g., the adenovirus type 5 E1 gene was used to immortalize the HEK 293 cell line; the Epstein-Barr virus can immortalize B lymphocytes by infection).
4. Artificial expression of key proteins required for immortality, for example, telomerase which prevents degradation of chromosome ends during DNA replication in eukaryotes
5. Hybridoma technology, specifically used for generating immortalized antibody-producing B cell lines, where an antibody-producing B cell is fused with a myeloma (B cell cancer) cell.

Table 13.1. Commonly Used Immortalized Cell Lines

Name	Cell Type and Origin	Comments
3T3	Mouse embryonic fibroblast	Robust and easy to handle; contact inhibited; stops growing at very high densities
HeLa	Human epithelial cell	From cervical cancer in a human patient named Henrietta Lacks; may contaminate other cultured cell lines; able to grow in suspension
COS	Monkey kidney	Efficiently transfected; commonly used as an expression system for high-level, short-term expression of proteins
293/293T/ HEK-293T	Human embryonic kidney	Easy to transfect and manipulate; commonly used as an expression system to study signalling and recombinant proteins
MDCK	Dog kidney epithelial cell	Polarized with distinct apical and basal sides, used in studying trafficking
CHO	Chinese hamster ovary	Useful for stable gene expression and high protein yields for biochemical assays; commonly used as an expression system for studying cell signalling and recombinant proteins
S2	Drosophila macrophage-like cells	Well-characterized Drosophila cell line; highly susceptible to RNAi treatment
PC12	Rat pheochromocytoma chromaffin cell	Neuron-like, derived from a neuroendocrine adrenal tumour; can differentiate into a neuron-like cell in the presence of NGF
Neuro-2a/ N2a	Mouse neuroblastoma	A model system for studying pathways involved in neuronal differentiation; can be driven to differentiate by cannabinoid and serotonin receptor stimulation

REFERENCES

1. Skloot R (2010), Immortal Life of Henrietta Lacks, the Random House, ISBN 978-0-307-71253-0, OCLC 974000732, retrieved 2020-09-20
2. Kaur G, Dufour JM (January 2012). “Cell lines: Valuable tools or useless artefacts”. Spermatogenesis. 2 (1): 1–5. doi:10.4161/mg.19885. PMC 3341241. PMID 22553484.
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5. Maqsood MI, Matin MM, Bahrami AR, Ghasroldasht MM (October 2013). “Immortality of cell lines: challenges and advantages of an establishment”. Cell Biology International. 37 (10): 1038–45. doi:10.1002/cbin.10137. PMID 23723166. S2CID 14777249.
6. http://sitn.hms.harvard.edu/flash/2020/vessels-for-collective-progress-the-use-of-hela-cells-in-covid-19-research/
7. Henle W, Henle G (1980). “Epidemiologic aspects of Epstein-Barr virus (EBV)-associated diseases”. Annals of the New York Academy of Sciences. 354: 326–31. doi:10.1111/j.1749-6632.1980.tb27975.x. PMID 6261650.

IMAGE REFERENCES

1. https://en.wikipedia.org/wiki/Immortalised_cell_line#:~:text=An%20immortalised%20cell%20line%20is,for%20prolonged%20periods%20in%20vitro.
2. https://en.wikipedia.org/wiki/Immortalised_cell_line#:~:text=An%20immortalised%20cell%20line%20is,for%20prolonged%20periods%20in%20vitro.
3. http://sitn.hms.harvard.edu/flash/2020/vessels-for-collective-progress-the-use-of-hela-cells-in-covid-19-research/